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Brain-heart interaction: direct and indirect circuits in health and diseases

Yi Wang1, Le-le Liu2, Tian-Ai Zhang2

  • 1School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China; The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.

Journal of Advanced Research
|April 8, 2026
PubMed

Insights

Cardiovascular and neurological diseases are increasingly linked. Understanding the brain-heart axis and its mediators offers new therapeutic strategies for managing these complex comorbidities.

Area of Science:

  • Neuroscience
  • Cardiology
  • Systems Biology

Background:

  • Rising comorbidity rates highlight the interconnectedness of cardiovascular and neurological diseases.
  • The brain-heart axis, involving neuroendocrine, neuroimmune, and autonomic pathways, is crucial in mediating this interaction.
  • Current siloed medical approaches inadequately address the pathological cycle of brain-heart interactions.

Purpose of the Study:

  • To review advancements in brain-heart crosstalk mechanisms over the last decade.
  • To explore neural pathways and regulatory mechanisms connecting the brain and heart.
  • To outline therapeutic potential for nervous system-targeted strategies in cardiac disease and vice versa.

Main Methods:

  • Systematic literature review of studies on brain-heart axis and cardiocerebral comorbidities.
  • Analysis of neuroendocrine, neuroimmune, and autonomic pathways involved in brain-heart crosstalk.
  • Synthesis of findings to propose new conceptual frameworks for treatment.

Main Results:

  • Identified key mediators of brain-heart crosstalk including the hypothalamic-pituitary-adrenal (HPA) axis, gut metabolites, extracellular vesicles (EVs), and the autonomic nervous system (ANS).
  • Delineated direct neural pathways and indirect regulatory mechanisms governing brain-heart interactions.
  • Highlighted the distinct roles of the brain-heart axis in various cardiovascular and psychiatric disorders.

Conclusions:

  • Targeting brain-heart axis mediators presents significant clinical potential for treating neurological and cardiovascular diseases.
  • Nervous system-targeted strategies offer promise for cardiac disease and neurological complications.
  • Optimizing cardiac function can modulate immune and endocrine pathways for managing cardio-cerebral comorbidities.
Abstract

Keywords:
Brain-heart axisCardiac dysfunctionNeuroendocrinologyNeuroimmunologyNeurological disorders

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